Studies on aspects of the molecular nature and biologic significance of the human equivalent of the Ia system will be continued. Certain of the alloantigenic variants already shown to be related to disease groups, including rheumatoid arthritis and multiple sclerosis, will be studied from the perspectives of structure, antigenic complexity, and relationship to stimulation in the mixed lymphocyte culture reaction. Antisera prepared in rabbits to highly purified human Ia like antigens will be used to characterize human lymphocyte populations. This will be correlated with a variety of other primary B and T cell markers. Particular emphasis will be placed on the relationship of unusual immunoglobulin determinants to cells that bear Ia like antigens but lack conventional membrane Ig. In addition the broader significance of the Ia like determinants as differentiation antigens in non lymphoid cells will be pursued. Here attention will be directed to the characteristics and significance of the determinants of myeloblasts, monocytes, and certain tumor cell lines.